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Qualitative and quantitative differences in the intensity of Fas-mediated intracellular signals determine life and death in T cells.

Authors
 Min-Jung Shin  ;  Jae-Hyuck Shim  ;  Jae-Young Lee  ;  Wook-Jin Chae  ;  Heung-Kyu Lee  ;  Tomohiro Morio  ;  Jun Han Park  ;  Eun-Ju Chang  ;  Sang-Kyou Lee 
Citation
 INTERNATIONAL JOURNAL OF HEMATOLOGY, Vol.92(2) : 262-270, 2010 
Journal Title
 INTERNATIONAL JOURNAL OF HEMATOLOGY 
ISSN
 0925-5710 
Issue Date
2010
Abstract
Fas stimulation has been reported to promote the activation and proliferation of T lymphocytes, but the intracellular signalling pathways that mediate non-apoptotic responses to Fas are poorly defined. To distinguish between the activation signalling and the death-inducing pathway downstream of Fas, we generated a novel T cell line expressing a chimeric hCD8-FasC protein and found that stimulation with the anti-CD8 antibodies induced tyrosine phosphorylation of TCR-proximal proteins, activation of Raf-1/ERK, p38 and JNK, and increased expression of CD69, Fas, and Fas ligand. Stimulation of hCD8-FasC-induced activation of an atypical NF-kappaB pathway, partial cleavage of caspases, and increased expression of TRAF1, FLIP(L) and FLIP(S), thereby protecting T cells from FasL-mediated apoptosis. The proliferative response transmitted through hCD8-FasC chimeric receptors was converted into death signals when cells were stimulated, resulting in increased expression of IL-2 and Nur77 and increased caspase cleavage. Surprisingly, both the enhanced expression of FLIP(L) and FLIP(S) and the complete inhibition of FLIP(S) expression were functionally associated with cell death induction. These findings imply that Fas is able to trigger intracellular signalling events driving both apoptosis and activation of T cells but that cell fate is determined by quantitative and qualitative differences in intracellular signalling following Fas stimulation.
DOI
10.1007/s12185-010-0637-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165735
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